Paper List
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STAR-GO: Improving Protein Function Prediction by Learning to Hierarchically Integrate Ontology-Informed Semantic Embeddings
This paper addresses the core challenge of generalizing protein function prediction to unseen or newly introduced Gene Ontology (GO) terms by overcomi...
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Incorporating indel channels into average-case analysis of seed-chain-extend
This paper addresses the core pain point of bridging the theoretical gap for the widely used seed-chain-extend heuristic by providing the first rigoro...
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Competition, stability, and functionality in excitatory-inhibitory neural circuits
This paper addresses the core challenge of extending interpretable energy-based frameworks to biologically realistic asymmetric neural networks, where...
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Enhancing Clinical Note Generation with ICD-10, Clinical Ontology Knowledge Graphs, and Chain-of-Thought Prompting Using GPT-4
This paper addresses the core challenge of generating accurate and clinically relevant patient notes from sparse inputs (ICD codes and basic demograph...
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Learning From Limited Data and Feedback for Cell Culture Process Monitoring: A Comparative Study
This paper addresses the core challenge of developing accurate real-time bioprocess monitoring soft sensors under severe data constraints: limited his...
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Cell-cell communication inference and analysis: biological mechanisms, computational approaches, and future opportunities
This review addresses the critical need for a systematic framework to navigate the rapidly expanding landscape of computational methods for inferring ...
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Generating a Contact Matrix for Aged Care Settings in Australia: an agent-based model study
This study addresses the critical gap in understanding heterogeneous contact patterns within aged care facilities, where existing population-level con...
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Emergent Spatiotemporal Dynamics in Large-Scale Brain Networks with Next Generation Neural Mass Models
This work addresses the core challenge of understanding how complex, brain-wide spatiotemporal patterns emerge from the interaction of biophysically d...
ATP Level and Phosphorylation Free Energy Regulate Trigger-Wave Speed and Critical Nucleus Size in Cellular Biochemical Systems
School of Physics, Center for Quantitative Biology, Peking University, Beijing 100871, China
30秒速读
IN SHORT: This work addresses the core challenge of quantitatively predicting how the cellular energy state (ATP level and phosphorylation free energy) governs the speed, direction, and critical initiation size of propagating biochemical trigger waves.
核心创新
- Methodology Develops a thermodynamically consistent reaction-diffusion framework that treats ATP concentration ([ATP]) and the nonequilibrium parameter γ (=[ATP]/(Keq[ADP][Pi])) as independent control variables for analyzing trigger waves.
- Biology Identifies the intracellular energetic state as a direct regulator of trigger-wave behavior, quantitatively linking metabolic conditions (ATP/ADP/Pi ratio) to spatiotemporal propagation dynamics.
- Theory Derives analytical expressions showing that the critical excitation radius (Rc) for sustained wave propagation depends on both [ATP] and γ, with scaling Rc ∝ 1/√[ATP] under specific approximations.
主要结论
- ATP concentration ([ATP]) and the phosphorylation free energy parameter (γ) jointly regulate trigger-wave speed (c0), with a dominant scaling c0 ∝ √[ATP] in the forward propagation regime.
- The sign of the potential difference (ΔF) between bistable states, determined by [ATP] and γ, dictates wave propagation direction (forward for ΔF<0, reverse for ΔF>0), with a stationary interface at ΔF=0.
- The critical nucleus radius (Rc) for sustained spherical wave propagation is inversely related to wave speed (Rc = D(d-1)/c0), leading to the prediction that higher [ATP] reduces the minimum trigger size required (Rc ∝ 1/√[ATP]).
摘要: Trigger waves are self-regenerating propagating fronts that emerge from the coupling of nonlinear reaction kinetics and diffusion. In cells, trigger waves coordinate large-scale processes such as mitotic entry and stress responses. Although the roles of circuit topology and feedback architecture in generating bistability are well established, how nonequilibrium energetic driving shapes wave propagation is less well understood. Here, we employ a thermodynamically consistent reaction–diffusion framework to investigate trigger-wave dynamics in ATP-dependent phosphorylation–dephosphorylation systems. We first recapitulate general expressions for trigger-wave speed in the bistable regime and analyze curvature-induced corrections that determine the minimum critical nucleus required for sustained propagation in higher dimensions. We then apply this framework to two representative systems, treating ATP concentration and the nonequilibrium parameter γ=[ATP]/(Keq[ADP][Pi]) as independent control variables to examine how energetic driving regulates wave propagation. Our results show that ATP and γ not only modulate wave speed, but can also reverse the direction of propagation and reshape the parameter regime supporting trigger waves. The critical excitation radius also depends on both ATP concentration and phosphorylation free energy. These findings identify the intracellular energetic state as a regulator of trigger-wave behavior, linking metabolic conditions to the spatial dynamics of wave propagation. More broadly, this framework connects classical reaction–diffusion theory with ATP-driven biochemical regulation and provides a general perspective on related energy-dependent cellular decision-making processes.